[A Meta-analysis of Pin1 gene polymorphism at -842 loci and cancer susceptibility].

Objective: Using Meta-analysis to evaluate the association between Pin1 gene polymorphism at -842 loci and cancer susceptibility. Methods: Pin1, polymorphism, tumor, variant and cancer as key words were used to systematically search for the case-control research on the association between the -842G/C polymorphisms of Pin1 and cancer susceptibility through China National Knowledge Infrastructure (CNKI), Wanfang Data, Embase and PubMed. The time of literatures was up to April 2(nd), 2019. Heterogeneity test, combined risk of cancer with the -842 C allele of Pin1, publication bias test and sensitivity analysis were performed by using Stata 12.0 software. Results: A total of 144 articles were retrieved. According to the inclusion criteria, a total of 11 articles were included (2 Chinese documents and 9 English documents). There were 5 667 cases and 6 120 controls in eligible articles. The heterozygous model showed that Pin1 (-842G/C) polymorphism was associated with cancer susceptibility, and the pooled OR (95%CI) value was 0.78 (0.61, 0.99). Subgroup analysis by cancer type suggested that the Pin1 (-842G/C) polymorphism could significantly decrease the incidence of breast cancer and lung cancer under the heterozygous model (GC vs GG), dominant model (GC+CC vs GG) and allele model (C vs G). The pooled OR (95%CI) values were 0.73 (0.58, 0.92), 0.71 (0.57, 0.89), and 0.73 (0.60, 0.89) in breast cancer and 0.64 (0.52, 0.78), 0.64 (0.53, 0.78), and 0.67 (0.55, 0.80) in lung cancer. The variant -842 C allele could significantly increase the risk of nasopharyngeal carcinoma under the homozygote model (CC vs GG) and recessive model (CC vs GG+GC). The pooled OR (95%CI) values were 2.22 (1.03-4.75) and 2.47 (1.16-5.26). No significant association was observed in squamous cell carcinoma. Conclusion: This Meta-analysis demonstrated that Pin1gene polymorphism at -842 was associated with cancer susceptibility.

Conversion of an inactive cardiac dihydropyridine receptor II-III loop segment into forms that activate skeletal ryanodine receptors.

A 25 amino acid segment (Glu666-Pro691) of the II-III loop of the alpha1 subunit of the skeletal dihydropyridine receptor, but not the corresponding cardiac segment (Asp788-Pro814), activates skeletal ryanodine receptors. To identify the structural domains responsible for activation of skeletal ryanodine receptors, we systematically replaced amino acids of the cardiac II-III loop with their skeletal counterparts. A cluster of five basic residues of the skeletal II-III loop (681RKRRK685) was indispensable for activation of skeletal ryanodine receptors. In the cardiac segment, a negatively charged residue (Glu804) appears to diminish the electrostatic potential created by this basic cluster. In addition, Glu800 in the group of negatively charged residues 798EEEEE802 of the cardiac II-III loop may serve to prevent the binding of the activation domain.

Effects of aging on phospholamban phosphorylation and calcium transport in rat cardiac sarcoplasmic reticulum.

Acceleration of cardiac relaxation upon beta adrenergic stimulation is due, in part, to enhancement in the rate of Ca2+ sequestration by the sarcoplasmic reticulum (SR) Ca2+ pump resulting from cAMP-mediated phosphorylation of the SR protein phospholamban. Our previous studies have shown that in rat myocardium, beta adrenergic activation of adenylate cyclase and the Ca2+ pump activity of SR decline with aging (Mech. Ageing Dev., 19 (1982) 127-139; 38 (1987) 127-143). In the present study, the effect of aging on phospholamban phosphorylation and consequent changes in SR Ca2+ pump activity were evaluated using cardiac SR from 6 (young adult), 12 (adult) and 28 (aged) months old rats. No age-related differences were observed in the rate or maximum level of phospholamban phosphorylation by exogenous cAMP-dependent protein kinase. The rates of ATP-dependent Ca2+ uptake by SR from young adult and aged rats were stimulated upon phospholamban phosphorylation, the percentage stimulation of Ca2+ uptake at varying Ca2+ concentrations (0.24-11.9 microM) was not diminished with aging. However, the rates of Ca2+ uptake by phosphorylated and unphosphorylated SR were remarkably lower (35-50%) in the aged. Regardless of the age of rats, the stimulatory effect of phosphorylation on Ca2+ uptake by SR was due to increase in Vmax of Ca2+ transport with no appreciable changes in K0.5 for Ca2+. These findings imply that in spite of the age-associated decline in SR Ca2+ pump activity, the ability of phospholamban to undergo cAMP-mediated phosphorylation and the relative responsiveness of the SR Ca2+ pump to phospholamban phosphorylation are not diminished in the aging heart.